疏血通联合甲钴胺治疗糖尿病周围神经病变疗效观察

目的观察疏血通联合甲钴胺治疗糖尿病周围神经病变（DPN）的疗效。方法76例患者随机分成治疗组和对照组,均予甲钴胺治疗。治疗组40例,给予6ml疏血通注射液及500μg的甲钴胺加入生理盐水250ml中静脉滴注,1次/d,共4周;对照组36例,单用500μg的甲钴胺静脉滴注,1次/d,共4周。结果治疗组临床症状改善明显,较对照组显著提高（P〈0.05）,神经传导速度也较对照组提高明显（P〈0.05）。结论疏血通与甲钴胺联合治疗糖尿病周围神经病变比单独实用甲钴胺效果好。     

疏血通与甲钴胺联合治疗糖尿病周围神经病变

目的观察疏血通针与甲钴胺联合治疗糖尿病周围神经病变(DPN)的疗效。方法将128例患者随机分为治疗组(66例)和对照组(62例),均以糖尿病教育,控制饮食,胰岛素严格控制血糖稳定基础上,治疗组给予疏血通针与甲钴胺针,对照组给予丹参与甲钴胺治疗,连用2周。结果治疗组DPN症状体征,神经传导速度改善明显高于对照组。结论疏血通针与甲钴胺针联用可明显改善DPN的治疗效果。     

前列地尔联合甲钴胺辅治糖尿病周围神经病变的疗效观察

目的观察前列地尔联合甲钴胺辅治糖尿病周围神经病变(DPN)的临床疗效。方法将DPN患者80例随机分成治疗组42例和对照组38例。在控制血糖基础上,对照组给予甲钴胺500μg肌内注射,每天1次,连续14d;治疗组在对照组治疗基础上加用前列地尔10μg+生理盐水100ml静脉滴注,每天1次,连续14d。观察2组临床疗效及治疗前后神经传导速度。结果治疗组总有效率为97.6%高于对照组的65.8%,差异有统计学意义(P<0.05)。2组治疗后正中神经和腓总神经运动传导速度(MCV)及感觉传导速度(SCV)均快于治疗前(P<0.05);且治疗组治疗后正中神经和腓总神经MCV及SCV均快于对照组(P<0.05)。结论前列地尔联合甲钴铵辅治DPN,对神经传导速度及症状、体征的改善均有良好作用,且无明显不良反应,值得推广应用。     

α-硫辛酸联合甲钴胺治疗2型糖尿病患者糖尿病周围神经病变的疗效观察

目的 观察α-硫辛酸联合甲钴胺治疗2型糖尿病患者糖尿病周围神经病变（DPN）的疗效.方法 符合入选条件的DPN患者68例,随机分为观察组与对照组,每组各34例.观察组给予α-硫辛酸600 mg/d静脉滴注及甲钴胺500μg/d静脉滴注,对照组给予甲钴胺500μg/d静脉滴注,共治疗3周.在治疗前、治疗后分别进行神经病变主觉症状问卷（TSS）评分及神经传导速度测定并观察有无药物不良反应.结果 组内比较：与治疗前相比,两组患者治疗后TSS评分均有下降（P＜0.01）,神经传导速度均有加快（P＜0.01）;组间比较：治疗后观察组患者TSS评分下降比对照组显著,两组比较差异有统计学意义（P＜0.05）,治疗后两组患者神经传导速度比较差异无统计学意义（P＞0.05）.两组均未见严重药物不良反应.结论 α-硫辛酸与甲钴胺联合治疗能有效且安全地治疗2型糖尿病患者DPN,联合治疗对DPN阳性症状的改善作用优于甲钴胺单药治疗.     

银杏达莫联合甲钴胺治疗糖尿病周围神经病变的疗效观察

目的观察银杏达莫注射液联合甲钴胺治疗糖尿病周围神经病变(DPN)的疗效。方法将102例DPN患者随机分成两组,治疗组50例,使用银杏达莫20 m L+0.9%盐水250 m L静滴,1次/天,甲钴胺500μg肌内注射,1次/天;对照组52例,甲钴胺500μg肌内注射,1次/天,疗程均为4周,记录患者治疗后主观症状、体征的改变及腓总神经传导速度。结果治疗后两组患者的临床疗效和神经传导速度均较治疗前明显改善,但以治疗组改善更为明显,两组间差异有统计学意义(P<0.05)。结论银杏达莫注射液联合甲钴胺治疗DPN优于单纯甲钴胺治疗,值得临床推广     

前列地尔联合甲钴胺治疗糖尿病神经病变的疗效观察

目的:观察前列地尔注射液联合甲钴胺治疗糖尿病周围神经病(DPN)的临床疗效。方法:将糖尿病并发神经病变的患者随机分为对照组38例和治疗组39例,两组均以降糖、降压、降脂等常规治疗,同时给予甲钴胺500μg静脉滴注,1次/d;治疗组加用前列地尔10μg加入氯化钠注射液10 ml静脉入小壶,1次/d。两组疗程均为2周。比较两组治疗前后症状、神经传导速度变化及临床疗效。结果:两组在治疗前后症状均有明显改善,治疗组有效率89.2%,对照组有效率63.2%,治疗组优于对照组(P<0.01),治疗过程中无明显不良反应。结论:前列地尔联合甲钴胺治疗糖尿病神经病变疗效肯定,安全性好。     

α-硫辛酸联合甲钴胺治疗糖尿病神经病变的疗效及对氧化应激、hs-CRP的影响

目的:观察α-硫辛酸(α-lipoic acid,ALA)联合甲钴胺治疗糖尿病神经病变(diabetic peripheral neuropathy,DPN)的疗效及对氧化应激、hs-CRP(high-sensitivity C-reactive protein)的影响。方法:将2型糖尿病合并DPN的患者120例随机分为2组,各60例。对照组:甲钴胺500μg+生理盐水100 mL静滴,qd。治疗组:在对照组的基础上加用ALA 0.6+生理盐水250mL静滴,qd,两组疗程共4周。观察治疗前后2组患者临床症状的改善、神经传导速度、hs-CRP、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malonaldehyde MDA)的变化,同时对2组患者治疗前后进行TSS评分。结果:经过4周的治疗,2组患者的TSS评分、hs-CRP均显著降低(P<0.05或P<0.01),神经传导速度明显增加(P<0.05),且治疗后2组间的TSS评分、hs-CRP、神经传导速度比较差异具有统计学意义(P<0.05)。对照组的SOD、MDA变化无明显差异(P>0.05),但与治疗前和对照组比较,治疗组的MDA明显下降(P<0.01或P<0.05),且SOD显著升高(P<0.01或P<0.05)。结论:ALA联合甲钴胺可显著改善DPN患者的临床症状,减轻氧化应激,同时更显著降低hs-CRP,疗效优于单独使用甲钴胺。     

甲钴胺联合参芎葡萄糖注射液治疗糖尿病周围神经病变的临床观察

目的:观察甲钴胺联合参芎葡萄糖注射液治疗糖尿病周围神经病变(DPN)的疗效和安全性。方法:将2010年5月-2011年2月收治的DPN患者78例随机均分为2组。对照组单用甲钴胺注射液1mg,静脉滴注,qd;治疗组在对照组基础上加用参芎葡萄糖注射液200mL,qd,14d为1个疗程。2组均治疗2个疗程。观察2组治疗前后血糖、尿蛋白、血肌酐、血液流变学指标、患侧腓总神经和胫神经运动传导速度及感觉传导速度等相关指标的变化及不良反应。结果:治疗组临床疗效及症状改善均优于对照组(P<0.05);治疗组血液流变学指标、患侧腓总神经和胫神经运动传导速度及感觉传导速度均较治疗前有显著改善(P<0.01),而对照组较治疗前无明显改善(P>0.05),治疗后2组比较差异有统计学意义(P<0.05)。2组均未见明显不良反应发生。结论:甲钴胺联合参芎葡萄糖注射液治疗DPN具有协同作用,疗效优于单用甲钴胺治疗,且未见明显副作用。     

黄芪注射液联用甲钴胺治疗糖尿病周围神经病变

目的:观察黄芪注射液联用甲钴胺治疗糖尿病周围神经病变(DPN)的疗效.方法:治疗组68例,给予黄芪注射液40 mL,加入0.9%氯化钠注射液250 mL,静脉滴注,qd,联用甲钴胺注射液500 μg,im,qd,疗程30 d;对照组24例,单用甲钴胺,用法、疗程同治疗组.观察两组对DPN患者腱、膝反射,自觉症状改变及对肌电图、空腹血糖(FBG)的影响.结果:治疗组显效率54.4%,对照组20.8%(P＜0.01);治疗组总有效率88.2%,对照组62.5%(P＜0.05);治疗后,治疗组的肌电图运动传导速度(MNCV)及感觉传导速度(SNCV)明显增加(P＜0.01),对照组增加(P＜0.05);治疗组FBG略有下降(P＞0.05).结论:黄芪注射液联用甲钴胺治疗DPN比单用甲钴胺疗效更好.     

丹参酮ⅡA磺酸钠联合甲钴胺治疗糖尿病周围神经病变30例疗效观察

目的：观察丹参酮ⅡA磺酸钠联合甲钴胺治疗糖尿病周围神经病变（DPN）的临床疗效。方法：60例DPN患者随机分为2组。治疗组30例给予丹参酮ⅡA磺酸钠60mg静脉滴注每日1次,甲钴胺500μg静脉注射每日1次。对照组30例给予甲钴胺500μg静脉注射每日1次,均为15天。结果：治疗组临床症状（疼痛、麻木、感觉异常）及反射检查较对照组改善明显(P<0.05或P<0.01),患者血流变学主要参数（红细胞压积、血浆粘度和纤维蛋白原）改善较对照组显著(P<0.05)。结论：丹参酮ⅡA磺酸钠联合甲钴胺治疗糖尿病周围神经病变较单用甲钴胺疗效更好。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.